Lipids Regulate Peripheral Serotonin Release Via Gut CD1d

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2023 Jun 24

PMID 37354904

Authors

Jialie Luo

Zuojia Chen

David Castellano

Bin Bao

Wenyan Han

Jian Li

Girak Kim

Dingding An

Wei Lu

Chuan Wu

Affiliations

Soon will be listed here.

Abstract

The crosstalk between the immune and neuroendocrine systems is critical for intestinal homeostasis and gut-brain communications. However, it remains unclear how immune cells participate in gut sensation of hormones and neurotransmitters release in response to environmental cues, such as self-lipids and microbial lipids. We show here that lipid-mediated engagement of invariant natural killer T (iNKT) cells with enterochromaffin (EC) cells, a subset of intestinal epithelial cells, promoted peripheral serotonin (5-HT) release via a CD1d-dependent manner, regulating gut motility and hemostasis. We also demonstrated that inhibitory sphingolipids from symbiotic microbe Bacteroides fragilis represses 5-HT release. Mechanistically, CD1d ligation on EC cells transduced a signal and restrained potassium conductance through activation of protein tyrosine kinase Pyk2, leading to calcium influx and 5-HT secretion. Together, our data reveal that by engaging with iNKT cells, gut chemosensory cells selectively perceive lipid antigens via CD1d to control 5-HT release, modulating intestinal and systemic homeostasis.

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